Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
  • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
  • C07D487/04—Ortho-condensed systems
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
  • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
  • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

• the present invention relates to new organic compounds possessing valuable pharmacological activity.
• the invention relates to imidazoquinoxalines of the structures: and wherein R 1 , R 5 , R 6 and R 7 are independently H, alkyl, aryl, alkenyl, alkynyl, hydroxy, hydroxyalkyl, alkoxy, mercapto, mercaptoalkyl, alkylthio, amino, alkylamino, aminoalkyl, carboxaldehyde, carboxylic acid and salts thereof, carbalkoxy, alkanoyl, cyano, nitro, halo, trifluoromethyl, sulfonyl, alkylsulfonyl, sulfonamido, or R 1 , R 5 , R 6' and R 7 may be taken together with the adjacent group to form a methylenedioxy group;
• alkyl groups in alkyl per se, hydroxyalkyl, alkoxy, aminoalkyl, alkylamino, alkylthio, mercaptoalkyl, alkanoyl, aralkyl, and carbalkoxy are preferably lower alkyl having from 1 to 8 carbon atoms, more preferably from 1 to 3 carbon atoms, and may be straight chain or branched.
• These groups include methyl, ethyl, propyl, isopropyl, sec-butyl, iso-amyl, hexyl, 2-ethylhexyl and the like.
• alkenyl and alkynyl groups may be straight chain or branched and preferably have 2 to 8 carbon atoms. These groups include vinyl, propenyl, ethynyl, propinyl and the like.
• R 6 and R 7 are independently H, alkyl, alkoxy, hydroxy, halo, trifluoromethyl or alkyl sulfonyl.
• the present new compounds of structure I are prepared by reductive ring closure of compounds of the formula: in which R is lower alkyl and R 1 , R 5 , R 6 and R 7 are as hereindefined, to produce compounds wherein R 4 is OH.
• Such compounds can be converted to those wherein R 4 is hydrogen by acylation with a lower alkanoic acid such as acetic acid and pivalic acid, and heating at high temperatures, e.g. above 200°C.
• R 4 is hydrogen
• substitution reactions wherein hydrogen is replaced by alkyl, alkenyl, alkynyl, aryl, aralkyl or alkanoyl by reaction of the corresponding halides.
• Other conversion and substitution reactions can be used to introduce groups representative of R 2' R 31 R 8 , R 71 R 6 , R 5 , and R 1 such as reduction of nitro to amino replacement of amino through diazonium salt replacement reactions, and the like.
• the present new compounds can also be converted to salts where basic and/or acid groups are present.
• Salts include those formed between basic nitrogen and acids, such as the commonly employed hydroholic acids, e.g. hydrochloric, sulfuric, benezenesulfuvic, toluenesulfonic and similar acids.
• the salts include those formed between free carboxy groups and metallic ions such as sodium, potassium, calcium and the like or ammonia and organic aminos, of course, the salts should be p harmaceuti- cally acceptable as well-known in this art.
• the procedures are generally carried out in the presence of a solvent such as dimethylformamide, dioxane, tetrahydrofuran, hydrocarbon solvents such as benzene and toluene, aqueous alcohols such as ethanol.
• a solvent such as dimethylformamide, dioxane, tetrahydrofuran, hydrocarbon solvents such as benzene and toluene, aqueous alcohols such as ethanol.
• the hydrochloride salt was prepared by treating the above free base in methanolic hydrogen chloride. After evaporation and washing with ethylacetate, the salt was obtained as a white solid, m.p. 210°C (dec).
• Certain compounds of the present invention e.g., those wherein X is O, S or imino while R 4 is H, or those wherein R 2 is OH or SH, can exist in both keto and enol forms and it is contemplated to include both classes of compounds in the scope of the present invention.
• the compounds of this invention are valuable for their cardiotonic activity. They are particularly valuable because the desirable inotropic activity is accompanied by only minimal changes in heart rate and blood pressure.
• Activity was measured in an open chest anaesthetized dog model. Drugs were administered intravenously in a polyethlene- glycol-200 suspension over a dose range of 0.1 to 100 mg/kg. Increases in contractile force of up to 49% with maximum increases of only 14% in heart rate were observed.
• the compounds can be administered orally in the form of elixirs, tablets and capsules or intraperitoneally, and it will be within the judgment of the physician to determine the optimum dosage and form of administration.

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• 1982
  • 1982-03-29 US US06/362,713 patent/US4440929A/en not_active Expired - Fee Related
  • 1982-07-14 EP EP82106315A patent/EP0070518A3/fr not_active Withdrawn
  • 1982-07-16 CA CA000407473A patent/CA1216291A/fr not_active Expired
  • 1982-07-16 NZ NZ201294A patent/NZ201294A/en unknown
  • 1982-07-16 AU AU86103/82A patent/AU561530B2/en not_active Ceased

Non-Patent Citations (3)

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